ABSTRACT Despite the Healthy People 2020 goal of 70.5%, colorectal cancer (CRC) screening rates in Federally Qualified Health Centers (FQHCs) are about 40%. The proposed study seeks to address this disparity and accelerate the adoption of effective cancer prevention and control screening practices to promote CRC screening. Leveraging our established community-academic network, which emphasizes participatory approaches among community, clinical, and academic stakeholders, we build on our extensive preparatory research that tested a low-literacy educational intervention plus Fecal Immunochemical Test [FIT]), and which resulted in initial screening rates of 80%. This work was primarily carried-out in urban-based settings. Prior research shows that repeat FIT screening rates often drop significantly without intervention and that there are notable geographic- related CRC disparities with higher mortality seen among individuals in rural areas. Additional research is needed to address repeat screening and expand our reach to other at-risk and rural populations. Informed by a community-based participatory research (CBPR) framework and enriched by implementation science approaches, CARES-REACH features a stepped wedge design with extension for maintenance to support an implementation strategy focused on multiple levels: organizational, provider, and patient level that entail processes to boost initial and repeat screening among average risk and age-eligible adults. This multilevel study entails implementation of a core set of evidence-based interventions (EBIs) that include: low literacy patient education (English, Spanish, and Haitian Creole language); provider education, system-wide electronic medical record (EMR) tools and prompts, and FIT distribution plus an organization-wide cancer control champion who motivates providers, navigates patients, and monitors system-wide screening activities. Specific aims are to: 1) implement an organization-wide multilevel CRC intervention using EBIs plus a cancer control champion in FQHCs located in rural and urban Central and Southwest Florida; 2) explore whether practice setting and population characteristics may differentially impact annual clinic CRC uniform Data system (UDS) screening rates; and 3) conduct a comprehensive evaluation of the implementation process (facilitators and impediments), resource requirements, and intermediate patient outcomes for the program in FQHC organizations. The intervention will be rolled out in a stepwise-method across clinics: one group of clinics receives early intervention roll-out and the other clinics are delayed to allow for rigorous comparison. The main outcome is change in annual clinic CRC screening rates compared to CRC screening rates of the prior year for each clinic as well as comparing screening rates among early roll-out clinics vs. delayed roll-out clinics. Addressing implementation processes will guide and direct scale-up to other FQHCs and community health systems.